Our experimental model for the progression of atherosclerotic lesions begins with endothelial injury and ends with the proliferation of smooth muscle cells. We suggest that prostaglandin metabolism is involved in endothelial injury, platelet aggregation and increased endothelial permeability as well as the proliferation of smooth muscle cells. This hypothesis will be examined first by studies on the biosynthesis of prostaglandins and thromboxane B2 in normal rabbit aorta. These metabolic studies will be correlated with studies on cholesteryl ester synthesis and hydrolysis in aorta. These metabolic studies will be applied in several model systems for endothelial injury and cell proliferation. The model systems include an in situ carotid artery preparation, an in vivo immune-complex protocol, and endothelial and smooth muscle cell culture systems. We are particularly interested in the effects of cholesterol, vitamin E and prostaglandin precursors, eicosa-8,11,14-trienoic acid and arachidonic (eicosa-5,8,11,14-tetraenoic) acid, on our model systems.